The University of California San Francisco (UCSF) has a long history of commitment to the treatment of children with brain tumors. Clinical and laboratory investigators in the Brain Tumor Research Center (BTRC) have over 25 years of experience in funded research of the biology and treatment of these diseases. Brain tumors are now the leading cause of cancer-related death in children. Currently available treatment for tumors such as brainstem glioma and malignant astrocytoma will not effectively control tumor growth for many of these children. In other types of brain tumors, treatment may control disease but will cause significant toxicity such as developmental and growth delay. For children who progress following initial therapy, few effective alternatives exist. Substantial gains for these children will only come about by an understanding of the biology of these diverse tumors, and the use of innovative treatment strategies based upon these data. Novel treatment approaches will require the expertise of physicians and researchers at institutions with the unique talents and resources available to employ these technologies. Clinical collaborations will be needed to efficiently conduct phase-I and II studies because of the small numbers of patients seen at various medical centers. UCSF has the physician talent, patient population, treatment and diagnostic resources, and Institutional commitment to collaborate with and achieve the goals of a Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC). We plan to utilize state of the art neuroimaging to diagnosis and monitor children with brain tumors. Advanced neurosurgical navigational techniques will be used for maximal tumor resection. Specialized methods of radiation therapy and unique drug therapy will be available, including but not limited to interstitial brachytherapy, radiosurgery, and experimental chemotherapy and gene therapy. Scientists in the BTRC will continue to use human tumor tissue to study the biology of childhood brain tumors, with the goal to translate this biologic information into newer, non-toxic, disease-specific treatments. UCSF will collaborate with the PBTCTC to achieve its Consortium goals, and contribute to its scientific agenda, taking a leadership role in study concept proposals and biologic studies. The aim of these treatment approaches is to increase disease-free and overall survival in children with brain tumors.